This research program intends to improve the therapy of a specific hematologic malignancy, namely multiple myeloma. New combinations of active drugs will be evaluated in a large number of patients. Improved treatments will be developed that enhance the frequency of response and the duration of remission in previously untreated patients. Different remission maintenance treatments will be evaluated in responding patients in order to reduce tumor mass maximally and to prolong remission duration. The incidence of reinduction of disease control in relapsing patients will also be investigated with various new agents. Tumor regression will be assessed from changes in myeloma protein production rate. The value of continued chemotherapy will be studied in patients with a constant tumor mass after different degrees of tumor reduction. The extent of disease will be defined in individual patients from a variety of clinical and laboratory parameters. The kinetics of tumor mass change during remission induction and relapse will be correlated with other evaluations of cell population kinetics using tritiated thymidine. Ancillary methods of therapy will be employed in order to improve the quality of response. The ultimate goal is adequate, long-term control of this malignant condition so that it no longer forms a major medical problem in man.